per protocol effects

"In summary, the similarities between follow-up studies with and without baseline randomization are becoming increasingly apparent as more randomized trials study the effects of sustained interventions over long periods in real world settings. What started as a randomized trial may effectively become an observational study that requires analyses that complement, but go beyond, intention-to-treat analyses. A key obstacle in the adoption of these complementary methods is a widespread reluctance to accept that overcoming the limitations of intention-to-treat analyses necessitates untestable assumptions. Embracing these more sophisticated analyses will require a new framework for both the design and conduct of randomized trials."